Related Experiment Video
Updated: Mar 11, 2026
08:02
Isolation of Primary Cancer-Associated Fibroblasts from a Syngeneic Murine Model of Breast Cancer for the Study of Targeted Nanoparticles
Published on: May 14, 2021
6.7K
Bioengineered ferritin-based lysosome-targeting chimera platform for tumor-targeted therapy
Shuai Zhang1,2,3, Yiliang Jin1,2, Yaxin Hou1
1CAS Engineering Laboratory for Nanozyme, State Key Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China.
Nature Communications
|March 10, 2026
Summary
A new modular platform using human heavy chain ferritin (HFn) enables efficient degradation of disease-related proteins. This versatile HFn-LYTAC system offers a promising strategy for targeted cancer therapies with good safety.
Area of Science:
- Biotechnology
- Molecular Biology
- Nanomedicine
Background:
- Lysosome-targeting chimeras (LYTACs) are emerging therapeutics for protein degradation.
- Current LYTAC development is often labor-intensive and lacks modularity.
- Targeting pathogenesis-associated proteins in lysosomes offers therapeutic potential.
Purpose of the Study:
- To develop a modular and efficient LYTAC platform.
- To leverage human heavy chain ferritin (HFn) for LYTAC construction.
- To enable targeted degradation of specific disease-associated proteins.
Main Methods:
- Engineered HFn scaffold with enhanced transferrin receptor 1 (TfR1) affinity.
- SpyTag-SpyCatcher system for conjugating target-specific affibodies to HFn.
- Utilized TfR1-mediated endocytosis for lysosomal delivery.
Main Results:
- Developed HFn-LYTACs efficiently degraded epidermal growth factor receptor (EGFR), EGFR-2, and programmed death-ligand 1 (PD-L1).
- Demonstrated dual degradation mechanisms: TfR1-dependent endocytosis and nanoparticle effects.
- Observed in vivo tumor growth inhibition with a favorable safety profile.
Conclusions:
- The modular HFn-LYTAC platform is versatile and efficient for protein degradation.
- This system shows promise for targeted cancer therapies.
- HFn-based LYTACs offer a novel strategy for lysosomal protein clearance.
